Method for making contact lenses having UV absorbing properties

ABSTRACT

A method for preparing a lens having UV-absorbing properties involves charging to a mold a monomer mixture comprising lens-forming monomers and an essentially non-UV-absorbing compound, and curing the monomer mixture to form a lens, followed by treating the lens to convert the essentially non-UV-absorbing compound to a UV-absorbing agent.

This is a divisional of application Ser. No. 09/079,781 filed on May 15,1998, now U.S. Pat. No. 5,914,355.

BACKGROUND OF THE INVENTION

The present invention relates to a method for preparing contact lensescontaining an ultraviolet-absorbing agent, and capable of absorbing UVradiation, wherein the lens-forming monomer mixture is cured by exposureto UV light.

Lenses such as contact lenses or intraocular lenses may include aUV-absorbing agent in the lens to absorb light in the ultraviolet regionof the spectrum, more particularly, to absorb light in the region ofabout 200 to 400 nm and, especially, about 290 to 400 nm. RepresentativeUV-absorbing materials for such lens applications are described in U.S.Pat. No. 4,304,895 (Loshaek), U.S. Pat. No. 4,528,311 (Beard et al.) andU.S. Pat. No. 4,719,248 (Bambury et al.).

Generally, such lenses are formed by free radical polymerization of amonomer mixture including desired lens-forming monomers, usually in thepresence of heat (thermal polymerization) or a light source(photopolymerization). One particular method for producing contactlenses involves thermal polymerization of the initial monomeric mixturein tubes in a heated water bath to provide rod-shaped articles, whichrods are then cut into buttons, the buttons then being lathed intocontact lenses; such methods for forming lenses including a UV absorbingagent are illustrated in the aforementioned U.S. Pat. No. 4,304,895(Loshaek) and U.S. Pat. No. 4,528,311 (Beard et al.). Other methodsinvolve casting the lenses directly in molds, wherein the monomermixture is charged to the mold and polymerized by exposure toultraviolet radiation.

In the case where it is desired to form lenses by a photopolymerizationprocess, UV curing (i.e., exposure of the monomer mixture to radiationmainly in the ultraviolet region) of the monomer mixtures has provedvery effective. It is also possible to effect photopolymerization usinga light source also including light in the visible region of thespectrum, although light in this region is generally less efficient ineffecting polymerization of conventional lens-forming monomer mixturesthan UV curing. However, for lenses including a UV absorbing agent,problems are encountered when attempting to cure the monomer mixturessince this agent absorbs UV light, thus diminishing the amount of UVlight available to effect polymerization and resulting in effective oruneven curing of the monomer mixture.

Accordingly, it would be desirable to provide a method whereby lensesexhibiting effective UV-absorbing properties can be polymerized byconventional free radical photopolymerization methods. The presentinvention provides such a method and solves the aforementioned problems.

SUMMARY OF THE INVENTION

The invention provides a method for preparing a lens having UV-absorbingproperties, comprising charging to a mold a monomer mixture comprisinglens-forming monomers and an essentially non-UV-absorbing compound, andcuring the monomer mixture to form a lens; and treating the lens toconvert the essentially non-UV-absorbing compound to a UV-absorbingagent.

Preferably, the lens is a contact lens or an intraocular lens, mostpreferably a hydrogel contact lens.

Preferred compounds included in the monomer mixture, and which areessentially non-UV absorbing but capable of converting to a UV-absorbingagent, are compounds of the formula: ##STR1## wherein each of R¹⁰, R¹¹and R¹² is independently hydrogen or a substituent; and

R¹⁵ is a protective radical that renders the compound essentiallynon-UV-absorbing. Especially preferred are compounds of the formulawherein at least one of R¹¹ and R¹² is a polymerizable ethylenicallyunsaturated radical, as well as compounds wherein R¹⁵ is --COCH₃.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The monomer mixtures employed in the invention include conventionallens-forming monomers.

The lens-forming monomers are monomers that are polymerizable by freeradical polymerization, generally including an activated unsaturatedradical, and most preferably an ethylenically unsaturated radical. (Asused herein, the term "monomer" denotes relatively low molecular weightcompounds that are polymerizable by free radical polymerization, as wellas higher molecular weight compounds that are polymerizable by freeradical polymerization and also referred to as "prepolymers","macromonomers", and related terms.)

An especially preferred class of materials are hydrogel copolymers. Ahydrogel is a crosslinked polymeric system that can absorb and retainwater in an equilibrium state. Accordingly, for hydrogels, the monomermixture will typically include at least one hydrophilic monomer and acrosslinking agent (a crosslinker being defined as a monomer havingmultiple polymerizable functionalities). Suitable hydrophilic monomersinclude: unsaturated carboxylic acids, such as methacrylic and acrylicacids; acrylic substituted alcohols, such as 2-hydroxyethylmethacrylateand 2-hydroxyethylacrylate; vinyl lactams, such as N-vinyl pyrrolidone;and acrylamides, such as methacrylamide and N,N-dimethylacrylamide.Typical crosslinking agents include polyvinyl, typically di- ortri-vinyl monomers, such as di- or tri(meth)acrylates ofdiethyleneglycol, triethyleneglycol, butyleneglycol and hexane-1,6-diol;divinylbenzene; and others known in the art.

Another preferred class of lens-forming monomers are those that formsilicone hydrogel copolymers. Such systems include, in addition to ahydrophilic monomer, a silicone-containing monomer. One suitable classof silicone containing monomers include known bulky, monofunctionalpolysiloxanylalkyl monomers represented by Formula (I): ##STR2##wherein: X denotes --COO--, --CONR⁴ --, --OCOO--, or --OCONR⁴ -- whereeach where R⁴ is H or lower alkyl; R³ denotes hydrogen or methyl; h is 1to 10; and each R² independently denotes a lower alkyl or halogenatedalkyl radical, a phenyl radical or a radical of the formula

    --Si(R.sup.5).sub.3

wherein each R⁵ is independently a lower alkyl radical or a phenylradical. Such bulky monomers specifically include methacryloxypropyltris(trimethylsiloxy)silane, pentamethyldisiloxanyl methylmethacrylate,tris(trimethylsiloxy) methacryloxy propylsilane,methyldi(trimethylsiloxy)methacryloxymethyl silane,3-[tris(trimethylsiloxy)silyl]propyl vinyl carbamate, and3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate.

Another suitable class are multifunctional ethylenically "end-capped"siloxane-containing monomers, especially difunctional monomersrepresented Formula (II): ##STR3## wherein: each A' is independently anactivated unsaturated group;

each R' is independently are an alkylene group having 1 to 10 carbonatoms wherein the carbon atoms may include ether, urethane or ureidolinkages therebetween;

each R⁸ is independently selected from monovalent hydrocarbon radicalsor halogen substituted monovalent hydrocarbon radicals having 1 to 18carbon atoms which may include ether linkages therebetween, and

a is an integer equal to or greater than 1. Preferably, each R⁸ isindependently selected from alkyl groups, phenyl groups andfluoro-substituted alkyl groups. It is further noted that at least oneR⁸ may be a fluoro-substituted alkyl group such as that represented bythe formula:

    --D'--(CF.sub.2).sub.s --M'

wherein:

D' is an alkylene group having 1 to 10 carbon atoms wherein said carbonatoms may include ether linkages therebetween;

M' is hydrogen, fluorine, or alkyl group but preferably hydrogen; and

s is an integer from 1 to 20, preferably 1 to 6.

With respect to A', the term "activated" is used to describe unsaturatedgroups which include at least one substituent which facilitates freeradical polymerization, preferably an ethylenically unsaturated radical.Although a wide variety of such groups may be used, preferably, A' is anester or amide of (meth)acrylic acid represented by the general formula:##STR4## wherein X is preferably hydrogen or methyl, and Y is --O-- or--NH--. Examples of other suitable activated unsaturated groups includevinyl carbonates, vinyl carbamates, fumarates, fumaramides, maleates,acrylonitryl, vinyl ether and styryl. Specific examples of monomers ofFormula (II) include the following: ##STR5## wherein: d, f, g, h and krange from 0 to 250, preferably from 2 to 100; and

M' is hydrogen or fluorine.

Other silicone-containing monomers include the silicone-containingmonomers described in U.S. Pat. Nos. 5,034,461, 5,610,252 and 5,496,871,the disclosures of which are incorporated herein by reference. Manyother silicone-containing monomers are well-known in the art.

As mentioned, polymerization (or curing) of monomer mixtures to formlenses by exposure of the monomer mixture to ultraviolet radiation hasproved very effective, however, for lenses including a UV-absorbingagent, problems are encountered when attempting to conductpolymerization of the monomer mixture by exposure to ultravioletradiation since this agent absorbs UV light. The invention provides amethod whereby lenses with UV-absorbing properties can be prepared byconventional methods involving free radical polymerization.

More specifically, to the monomer mixture including the lens-formingmonomers is added a compound that is essentially non-UV-absorbing butcan subsequently be converted to a UV absorbing agent in apost-polymerization process, i.e., after the lens has been cured, forexample, photopolymerized by UV curing. As used herein, the term"UV-absorbing agent" denotes an agent that, when incorporated in a filmof the lens-forming monomers having a 0.02-mm thickness, is capable ofreducing the transmittance of light in the region of 320 to 400 nm to atleast 50 percent of a similar sample lacking the UV-absorbing agent, andpreferably, to at least 70 percent, most preferably to at least 85percent. It is also preferred that such a sample incorporating theUV-absorbing agent transmits no more than 70% of light in the region of320 to 400 nm and no more than 90% of light in the region of 290 to 320nm. The term "essentially non-UV-absorbing agent" denotes an agent that,if incorporated in such a film sample, is capable of reducing thetransmittance of light in the region of 320 to 400 nm to no more than 40percent of a similar sample lacking this agent (and preferably, no morethan that 20 percent).

One preferred class of UV-absorbing agents known for contact lens andintraocular lens applications includes benzotriazoles that contain aphenol moiety. Examples of such benzotriazoles are described in U.S.Pat. No. 4,528,311 (Beard et al.), U.S. Pat. No. 4,716,234 (Dunks etal.), U.S. Pat. No. 4,719,248 (Bambury et al.), U.S. Pat. No. 3,159,646(Milionis et al.) and U.S. Pat. No. 3,761,272 (Manneus et al.), thedisclosures of which are incorporated herein by reference. Specificexamples include2-(2'-hydroxy-5'-methacrylamidophenyl)-5-chlorobenzotriazole,2-(2'-hydroxy-5'-methacrylamidophenyl)-5-methoxybenzotriazole,2-(2'-hydroxy-5'-methacryloxypropyl-3'-t-butyl-phenyl)-5-chlorobenzotriazole,2-(2'-hydroxy-5'-methacryloxyethylphenyl)benzotriazole,2-(2'-hydroxy-5'-methacryloxypropylphenyl)benzotriazole. Thesebenzotriazoles may be represented by the general formula (I): ##STR6##wherein R¹⁰ may be hydrogen or a substituent (representativesubstituents being selected from the group consisting of halogen, C₁ -C₄alkyl and C₁ -C₄ alkoxy); and

each of R¹¹ and R¹² independently may be hydrogen or a substituent(representative substituents being selected from the group consisting ofhalogen, C₁ -C₄ alkyl and C₁ -C₄ alkoxy). Preferably, at least one ofR¹¹ or R¹² is a polymerizable ethylenically unsaturated moiety, such as

    --R.sup.13 --X--CO--C(R.sup.14)═CH.sub.2

wherein R¹³ is a single bond or C₁ -C₁₀ alkylene, X is --O-- or --NH--,and R¹⁴ is hydrogen or methyl.

The essentially non-UV-absorbing agent that is actually incorporated inthe initial monomer mixture, along with the lens-forming monomers, is aderivative of the UV-absorbing agent where the hydroxyl radical of thephenol moiety is replaced with a protective group, such protective grouprendering the agent essentially non-UV absorbing (i.e., the protectivegroup essentially shifts the absorption properties of the compound sothat the agent does not absorb as strongly in the 320 to 400 nm range).This protective group can be converted back to a hydroxyl radical afterthe lens is cured, thus rendering the lens UV-absorbing.

For the preferred benzotriazoles, the agents that are derivatives of theFormula (I) compounds and that are added to the initial monomer mixture,may be represented by the general formula (Ia): ##STR7## wherein R¹⁰,R¹¹ and R¹² have the same meanings as for Formula (I) and R¹⁵ is theprotective group that can be converted back to the hydroxyl radical in apost-polymerization treatment process. Preferably, at least one of R¹¹or R¹² in Formula (Ia) is a polymerizable ethylenically unsaturatedmoiety, such as

    --R.sup.13 --X--CO--C(R.sup.14)═CH.sub.2

Specific examples of the --R¹⁵ radical include: acetyl (--COCH₃),alkylsilanes such as --O--Si(CH₂ CH₃)₃ ; alkyl ethers such as methoxy;and alkyl esters, such as methylcarbonyloxy and methycarbonate. It isunderstood, however, that any suitable phenol protecting radicalavailable in the art may be used.

The agents of Formula (Ia) may be prepared by methods generally known inthe art. In the case where the protective group is --COCH₃, a compoundof Formula (I) can be reacted with acetic anhydride. In the case wherethe protective group is an alkyl silane, a compound of Formula (I) canbe reacted with a chlorotrialkylsilane, such as chlorotriethylsilane. Inthe case where the protective group is an alkyl ether, a compound ofFormula (I) can be reacted with chloroalkylether, such as chloromethylmethyl ether. In the case where the protective group is analkylcarbonate, a compound of Formula (I) can be reacted withvinylchloroformate. Representative detailed syntheses of the Formula(Ia) compounds is provided in the examples, below.

Another representative class of UV-absorbing agents are benzophenoneUV-absorbers containing a phenolic radical. Specific examples are2,2-dihydroxy-4,4-dimethoxy-benzophenone,2,2-dihydoxy-4-methoxy-benzophenone, and the polymerizable benzophenonesdescribed in U.S. Pat. No. 4,304,895 (Loshaek) the disclosure of whichis incorporated herein by reference. Accordingly, the derivatives ofthese UV-absorbing agents, that are incorporated in the initial monomermixture in practice of this invention, are benzophenone derivativeswhere at least one hydroxyl radical of the phenolic radical is replacedwith one of the aforementioned protective groups, for example, an acetylradical.

Especially preferred for contact lens and intraocular lens applicationsare agents that include a polymerizable ethylenically unsaturatedmoiety. For example, as mentioned for the benzotriazoles of Formula(Ia), preferred agents include those with at least one ethylenicallyunsaturated radical. These agents copolymerize with the lens-formingmonomers, i.e., the agent forms an integral part of the copolymernetwork. Surprisingly, it has been found that even though thesecompounds copolymerize with the lens-forming monomers, the protectedradical is still able to be converted back to a phenolic moiety, thusrendering the compounds effective as UV-absorbing agents.

The agents convertible to UV-absorbing agents will generally be includedin the monomer mixture at about 0.1 to about 5 weight percent, morepreferably about 0.2 to about 2 weight percent.

The monomer mixtures may further include a tinting agent that impartssome degree of color to the lens. The monomer mixtures will generallyinclude a polymerization initiator, such as commercialacetophenone-based initiators, titanocene-based initiators, and/oraromatic phosphine oxide-based initiators available under the Darocur orIrgacur tradenames.

Generally, the monomer mixture, containing the lens-forming monomers andthe protected essentially non-UV-absorbing agent, is charged to a mold,and then subjected to light to effect curing of the monomer mixture inthe mold. Various processes are known for curing a monomeric mixture inthe production of contact lenses, including spincasting and staticcasting. Spincasting methods involve charging the monomer mixture to amold, and spinning the mold in a controlled manner while exposing themonomer mixture to light. Static casting methods involve charging themonomer mixture between two mold sections, one mold section shaped toform the anterior lens surface and the other mold section shaped to formthe posterior lens surface, and curing the monomer mixture by exposureto light. Such methods are described in U.S. Pat. Nos. 3,408,429,3,660,545, 4,113,224, 4,197,266, and 5,271,875.

Following casting of the lenses, the cured lens is treated to remove thephenol protective group, i.e., to convert this radical to hydroxyl.Various methods can be used to carry out this "deprotection" process,examples including: immersing the lens in a borate-buffered solution;immersing the lens in a saturated bicarbonate solution; or immersing thelens in a solution of bicarbonate and lower alcohol. If desired, thistreatment can be conducted at elevated temperature to decrease timerequired for the treatment. A further advantage of the invention is thatthis deprotection post-treatment can be accomplished by heating the lenswhile immersed in a buffered saline solution, a process that isconventionally performed on contact lenses as part of the sterilizationprocess, thereby avoiding the need for a supplemental step in theoverall manufacturing process.

The following examples illustrate various preferred embodiments.

EXAMPLE 1

Synthesis of acetyl Protected2-[3-(2H-Benzotriazol-2-yl)-4-hydroxyphenyl]ethyl Methacrylate

To a 250 mL one-neck round bottom fitted with a magnetic stirrer isadded (20.0 g, 0.192 mmole), acetic anhydride (50 g, mole) anddimethylaminopyridine (10.4 g, 68.0 mmol). The reaction is stirred for48 hours at which time 200 ml of ethyl acetate is added and the solutionis washed five times with brine. The organic layer is collected, driedover magnesium sulfate, filtered and rotoevaporated to an oil using anair bleed and a maximum temperature of 40 C. to minimize polymerformation. The oil is purified by fractional column chromatography (250g silica gel/methylene chloride as eluant) resulting in 16.5 g (purityof 99.0% by liquid chromatography) of acetyl protected2-[3-(2H-Benzotriazol-2-yl)-4-hydroxyphenyl]ethyl methacrylate.

EXAMPLE 2

UV Spectra Data

The UV spectra of the compound prepared in Example 1 was compared withthe UV spectra of its parent compound (a compound of Formula (I),2-(2'-hydroxy-5'-methacryloxyethylphenyl)benzotriazole)) by dilutingeach compound in a solvent at a 1:100,000 dilution ratio, and measuringthe amount of light absorption. Whereas the parent compound exhibited asharp absorption peak at about 350 nm, the compound of Example 1exhibited no such peak, instead having a well-defined absorption peak atabout 300 nm, indicating that addition of the acetyl-protective groupwas effective at shifting significantly the UV absorbance to a lowerwavelength.

EXAMPLE 3

The compound of Example 1 was added at 0.8 weight percent to a monomermixture of 2-hydroxyethylmethacrylate (Hema),ethyleneglycoldimethacrylate (EGDMA, a crosslinker), benzoin methylether (BME, an initiator) and glycerin (a diluent). For comparativepurposes, the compound2-(2'-hydroxy-5'-methacryloxyethylphenyl)benzotriazole) was added at 0.8weight percent to the same base monomer mixtures. Both resultantmixtures were cast between two glass plates and exposed to UV light(2500 μW/cm²) for one hour. Whereas the mixture containing the compoundof Example 1 was effectively polymerized within 10 minutes to form afilm, the comparative mixture, containing the conventional UV-absorbingagent, failed to polymerize.

EXAMPLE 4

The compound of Example 1 was added at 0.4 weight percent and 0.8 weightpercent to same Hema-based monomer mixture described in Example 3. Bothresultant mixtures were cast between two glass plates and exposed to UVlight (2500 μW/cm²) for one hour. The resultant cured films weresubjected to a series of deprotection schemes, including: autoclaving inborate-buffered solution; autoclaving in saturated bicarbonate; soakingin saturated bicarbonate solution at room temperature; and soaking in50/50 solution of methanol/saturated bicarbonate. The treated films werecompared with a film prepared by thermal curing the compound2-(2'-hydroxy-5'-methacryloxyethylphenyl)benzotriazole) (0.8 weightpercent) added to the same base monomer mixture. For all treated films,the acetyl group was effectively removed, as these films had UVabsorbing properties characteristic of the thermally cured films basedon the UV absorbing parent compound.

EXAMPLE 5

The compound of Example 1 was added at 0.8 weight percent (wt %) to amonomer mixture composed mainly of the following: 20 wt % of afumarate-capped polysiloxanediol-based prepolymer (Formula (IIc) whereinh is about 20); 40 wt % methacryloxypropyl tris(trimethylsiloxy)silane;and 40 wt % N,N-dimethylacrylamide. The resultant mixture was castbetween two glass plates and exposed to UV light (2500 μW/cm²) for onehour. The resultant cured films were subjected to a series ofdeprotection schemes as in Example 4. It was found that soaking in 50/50solution of methanol/saturated bicarbonate successfully converted thecompound to a UV-absorbing agent.

EXAMPLE 6

The compound of Example 1 was added at 0.8 weight percent to a monomermixture composed mainly of 2-hydroxyethylmethacrylate,N-vinylpyrrolidone, crosslinking monomers and4-t-butyl-2-hydroxycyclohexylmethacrylate. The resultant mixture wasplaced on the molding surface of a first plastic mold section, shaped toprovide an anterior contact lens surface, and a second plastic moldsection having a molding surface shaped to provide a posterior contactlens surface was placed on the first mold section, the monomer mixturebeing contained in the mold cavity formed between these two moldingsurfaces. This assembly was then subjected to UV curing. The two moldsections were then immediately separated, lenses were released from themold section, and equilibrated in borate buffered saline. Uponautoclaving, the compound was converted to a UV-absorbing agent, as thelenses exhibited UV absorbing properties.

Many other modifications and variations of the present invention arepossible to the skilled practitioner in the field in light of theteachings herein. It is therefore understood that, within the scope ofthe claims, the present invention can be practiced other than asspecifically described.

We claim:
 1. A compound of the formula: ##STR8## wherein each of R¹⁰,R¹¹ and R¹² is independently hydrogen or a substituent selected from thegroup consisting of halogen, C₁ -C₄ alkyl and C₁ -C₄ alkoxy, providedthat at least one of R¹¹ and R¹² is a polymerizable ethylenicallyunsaturated radical of the formula --R¹³ --X--CO--C(R¹⁴)═CH₂.
 2. Thecompound of claim 1, wherein R¹⁵ is --COCH₃.